scholarly journals SOMATOSTATIN (SST) PROMOTER HYPERMETHYLATION IN ASSOCIATION WITH COLORECTAL CANCER

2020 ◽  
Vol 17 (36) ◽  
pp. 1075-1082
Author(s):  
Mohammed FAWZI ◽  
Ahmed TAIFI ◽  
Zahraa Kamil Kadhim LAWI
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Cancer Progression ◽  
Early Stage ◽  
Promoter Hypermethylation ◽  
Healthy Controls ◽  
Dna Hypermethylation ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Common Diagnosis

Colorectal cancer (CRC) is one of the most common diagnosis malignancies with different risk factors, including environmental and genetic. Several genes, called tumor suppressor genes, play an essential role in inhibiting these risk factors by preventing tumor development. One of these genes is somatostatin (SST). Somatostatin is an antiproliferative peptide with pro-apoptotic effects that enhance cell death to prevent tumor growth. This study aimed to investigate the association relationship between DNA methylation in SST promotor and colorectal cancer progression. After DNA bisulfite conversion, SST promoter methylation was examined using quantitative methylation‐specific PCR (qMSP) in 71 cases (19 metastasis CRC, 28 early-stage CRC, and 24 healthy controls). Quantitative methylation‐specific PCR (qMSP) is a real-time PCR method used to determine the unmethylated and methylated cytosine residues using a specific set of primers. The percentage of hypermethylation in SST promoter was 17%, 60%, and 79% for healthy controls, early-stage, and metastasis CRC groups. The results showed a significant association between DNA hypermethylation of SST promoter and CRC progression. P-values were 0.0364 for the early-stage group and 0.0138 for the metastasis group. The results also supported that the DNA hypermethylation block the expression of SST, which in turn induce carcinogenesis. The detection of SST promoter hypermethylation at early stage of cancer could be used as a biomarker for screening and prognosis of CRC.

scholarly journals Characterization of Cell Free Plasma Methyl-DNA From Xenografted Tumors to Guide the Selection of Diagnostic Markers for Early-Stage Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Ling Liu ◽  
Jinghua Feng ◽  
Julian Polimeni ◽  
Manli Zhang ◽  
Hai Nguyen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Human Tumor ◽  
Restriction Enzyme Digestion ◽  
Healthy Controls ◽  
Sequence Specificity ◽  
Lung Cancers ◽  
Specific Pcr ◽  
Tumor Origin ◽  
Species Specific

Circulating cell-free methyl-DNA (mcfDNA) contains promising cancer markers but its low abundance and possibly diverse origin pose challenges toward the accurate diagnosis of early stage cancers. By whole-genome bisulfite sequencing (WGBS) of cell-free DNA (cfDNA) from about 0.5 mL plasma of mice xenografted with human tumors, we obtained and aligned the reads to the human genome, filtered out the mouse and carrier bacterial sequences, and confirmed the tumor origin of methyl-cfDNA (mctDNA) by methylation-sensitive restriction enzyme digestion prior to species-specific PCR. We estimated that human tumor-specific reads (ctDNA) or mctDNA comprised about 0.29 or 0.01%, respectively of the xenograft mouse cfDNA, and about 0.029 or 0.001% of the cfDNA of human early stage cancer patients. Similar WGBS of early stage (0-II, node- and metastasis-free) breast, lung or colorectal cancer samples identified hundreds of specific DMRs (differentially methylated regions) compared to healthy controls. Their association with tumourigenesis was supported by stage-dependent methylation, tumor suppressor or oncogene clusters, and genes also identified in the xenograft samples. Using 20 three-cancer-common and 17 colorectal cancer-specific DMRs in combination (top 0.0018% of the WGBS methylation clusters) was sufficient to distinguish the stage I colorectal cancers from breast and lung cancers and healthy controls. Our data thus confirmed the tumor origin of mctDNA by sequence specificity, and provide a selection threshold for authentic tumor mctDNA markers toward precise diagnosis of early stage cancers solely by top DMRs in combination.

scholarly journals Assessment of Aberrant Promoter Hypermethylation of RASSF1a and P16 in Endometrial Carcinoma

2021 ◽  
Vol 8 (7) ◽  
pp. 402-409
Author(s):  
Nagaratna Shivanandappa ◽  
Shalini N Swamy ◽  
Sandeep Kumar S
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Promoter Hypermethylation ◽  
Pathological Examination ◽  
Clinicopathological Parameters ◽  
P Value ◽  
Dna Hypermethylation ◽  
Chi Square ◽  
Methylation Specific Pcr ◽  
Specific Pcr

Endometrial carcinoma is one of the most common gynecological malignancies known to affect around 142000 women worldwide. Aberrant promoter hypermethylation of tumor suppressor genes is a common epigenetic alteration reported in cancers. In the present study we report the aberrant promoter hypermethylation of RASSF1a and p16 in 78 endometrial cancer patients. Methods: Endometrial carcinoma samples were collected after pathological examination and DNA was extracted. The DNA was subjected to sodium bisulfite modification and then used to perform methylation specific PCR. The PCR was performed using a two step procedure of nested and methylation specific PCR. The PCR product was visualized using agarose gel electrophoresis. The results obtained were correlated with various clinicopathological parameters. Chi square test was used for statistical analysis and a p-value of <0.05 was considered statistically significant. Result: 60 of the 78 (76.92%) samples showed methylation for RASSF1a gene. 28 of the 78 (35.8%) samples showed methylation for p16 gene. A higher methylation frequency was observed for RASSF1a in the endometrioid and poorly differentiated histological subtypes and stage I and II of the disease. Conclusion: Aberrant promoter hypermethylation of RASSF1a and p16 is known to play an important role in endometrial cancer initiation and progression. The methylation patterns can be used as an important molecular marker for early diagnosis and prognosis of endometrial cancer. Keywords: Epigenetic alterations, DNA Hypermethylation, Endometrial cancer, RASSF1a, p16, Methylation-specific PCR.

scholarly journals Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Jing-dong Zhou ◽  
Ting-juan Zhang ◽  
Zi-jun Xu ◽  
Zhao-qun Deng ◽  
Yu Gu ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Myelodysplastic Syndromes ◽  
Bisulfite Sequencing ◽  
De Novo ◽  
Dna Hypermethylation ◽  
Reduced Representation ◽  
Targeted Bisulfite Sequencing ◽  
Specific Pcr ◽  
Genome Wide ◽  
Potential Biomarker

AbstractThe potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.

scholarly journals Risk factors in the recurrence of the colorectal cancer

2002 ◽  
Vol 49 (2) ◽  
pp. 40-43 ◽  
Author(s):  
J. Ulanska ◽  
A. Dziki ◽  
W. Langner
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Rectal Cancer ◽  
Local Recurrence ◽  
Early Stage ◽  
Concomitant Treatment ◽  
Preventive Chemotherapy ◽  
Tnm System ◽  
Definition Of ◽  
Colorectal Cancer Patients

Traditionally, the clinical outcome of colorectal cancer patients may be predicted by pathological staging by either Dukes staging or the UICC-TNM system. However, some of Dukes stage A (approximately 10% of patients) and Dukes B patients (30-40%) will develop local recurrence or distant metastasis years after receiving standard surgical treatments. Therefore it is important to find some other indicators that can predict for recurrence so that we can screen for high-risk early-stage patients who may need preventive chemotherapy or other adjuvant therapy. The aim of this study is determination of risk factor for local recurrence in rectal cancer. In this study there has been used and summarized also research records and publications from different clinical hospitals according to actual international literature. Part of elements connected with patient, tumor and genetic and immunological factors remains independent on curative procedures. However better investigation these factors might affect on therapy, frequency of follow-up examinations, and help to detect recurrence at very early phase. Concomitant treatment factors are able to be moderate by surgeons and therapeutics. Therefore precise definition of risk factors might be helpful in decrease recurrence rate in patients with rectal cancer.

scholarly journals Detection of Colorectal Cancer in Circulating Cell-Free DNA by Methylated CpG Tandem Amplification and Sequencing

2019 ◽  
Vol 65 (7) ◽  
pp. 916-926 ◽  
Author(s):  
Jingyi Li ◽  
Xin Zhou ◽  
Xiaomeng Liu ◽  
Jie Ren ◽  
Jilian Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Plasma Samples ◽  
Dna Hypermethylation ◽  
Cell Free Dna ◽  
Noncancerous Tissue ◽  
Clinical Sensitivity ◽  
Free Dna ◽  
A Genome ◽  
Circulating Cell Free Dna

Abstract BACKGROUND Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-wide DNA hypermethylation analysis technique using circulating cell-free DNA (cfDNA) is attractive for the noninvasive early detection of CRC and discrimination between CRC and other cancer types. METHODS We applied the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, with a fully methylated molecules algorithm, to plasma samples from patients with CRC (n = 147) and controls (n = 136), as well as cancer and adjacent noncancerous tissue samples (n = 66). We also comparatively analyzed plasma samples from patients with hepatocellular carcinoma (HCC; n = 36). RESULTS Dozens of DNA hypermethylation markers including known (e.g., SEPT9 and IKZF1) and novel (e.g., EMBP1, KCNQ5, CHST11, APBB1IP, and TJP2) genes were identified for effectively detecting CRC in cfDNA. A panel of 80 markers discriminated early-stage CRC patients and controls with a clinical sensitivity of 74% and clinical specificity of 90%. Patients with early-stage CRC and HCC could be discriminated at clinical sensitivities of approximately 70% by another panel of 128 markers. CONCLUSIONS MCTA-Seq is a promising method for the noninvasive detection of CRC.

scholarly journals Diagnostic and Prognostic Value of B4GALT1 Hypermethylation and Its Clinical Significance as a Novel Circulating Cell-Free DNA Biomarker in Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1598 ◽  
Author(s):  
Francesco Picardo ◽  
Antonella Romanelli ◽  
Laura Muinelo-Romay ◽  
Tommaso Mazza ◽  
Caterina Fusilli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lung Metastases ◽  
Methylation Status ◽  
Therapy Response ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Aberrant Expression ◽  
Predictive Values ◽  
Methylation Specific Pcr ◽  
Specific Pcr

Epigenetic modifications of glyco-genes have been documented in different types of cancer and are tightly linked to proliferation, invasiveness, metastasis, and drug resistance. This study aims to investigate the diagnostic, prognostic, and therapy-response predictive value of the glyco-gene B4GALT1 in colorectal cancer (CRC) patients. A Kaplan–Meier analysis was conducted in 1418 CRC patients (GEO and TCGA datasets) to assess the prognostic and therapy-response predictive values of the aberrant expression and methylation status of B4GALT1. Quantitative methylation-specific PCR (QMSP) and droplet digital quantitative methylation-specific PCR (dd-QMSP) were respectively used to detect hypermethylated B4GALT1 in metastasis and plasma in four cohorts of metastatic CRC cases (mCRC). Both the downregulated expression and promoter hypermethylation of B4GALT1 have a negative prognostic impact on CRC. Interestingly a low expression level of B4GALT1 was significantly associated with poor cetuximab response (progression-free survival (PFS) p = 0.01) particularly in wild-type (WT)-KRAS patients (p = 0.03). B4GALT1 promoter was aberrantly methylated in liver and lung metastases. The detection of hypermethylated B4GALT1 in plasma of mCRC patients showed a highly discriminative receiver operating characteristic (ROC) curve profile (area under curve (AUC) value 0.750; 95% CI: 0.592–0.908, p = 0.008), clearly distinguishing mCRC patients from healthy controls. Based on an optimal cut-off value defined by the ROC analysis, B4GALT1 yield a 100% specificity and a 50% sensitivity. These data support the potential value of B4GALT1 as an additional novel biomarker for the prediction of cetuximab response, and as a specific and sensitive diagnostic circulating biomarker that can be detected in CRC.

A multiplex methylation-specific PCR assay for the detection of early-stage ovarian cancer using cell-free serum DNA

2013 ◽  
Vol 130 (1) ◽  
pp. 132-139 ◽  
Author(s):  
Qing Zhang ◽  
Guohong Hu ◽  
Qifeng Yang ◽  
Ruifen Dong ◽  
Xing Xie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Early Stage ◽  
Pcr Assay ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Serum Dna ◽  
Specific Pcr Assay ◽  
Free Serum ◽  
Early Stage Ovarian Cancer
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